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foods. This supposition must consider that
some (perhaps many) biological effects of
polyphenols could not necessarily be linked
to their antioxidant capacity. In conjunc-
tion, these recent studies suggest that ROS
are only a part of the picture and it seems
that ageing is a highly regulated process,
when apparently each individual or species
has an 'expiration date'. Therefore, if we
want to extend this 'expiration date' by con-
suming antioxidants we must keep in mind
that this only represents a little help.
HO
H
H
OH
3
C
H
3
C
OH
O
O
H
3
C
H
O
O
O
O
OH
3
C
HO
H
3
C
O
OMe
H
3
C
2.2 Changing the Viewpoint:
the Ying and Yang of Antioxidant
Molecules
Fig. 2.1.
The structure of rapamycin.
some TOR mutants (Bjedov
et al.
, 2010).
Moreover, Harrison
et al
. (2009, 2010) found
an increase in lifespan when rapamicyn
was administrated to genetically heteroge-
neous mice.
The mutation of a single gene in chro-
mosome 13 causes an extensive ageing phe-
notype including arteriosclerosis and ataxia,
and vascular calcification (Kuro-o, 2000,
2001, 2007, 2009, 2010a,b). This gene was
called Klotho and, conversely, its over
expression extended lifespan in mice. The
Klotho protein functions as a hormone that
represses intracellular signals of insulin and
insulin-like growth factor (IGF-1), and
attenuates ageing. As a hormone, Klotho
could circulate and many functions have
been described. Among them, this hormone
could regulate the production of nitric
oxide, the p53/p51 pathway, reduce the
angiotensin II-induced ROS production,
inhibit Wnt signalling and increase resist-
ance to oxidative stress (Wang and Sun,
2009). Klotho is only expressed in some tis-
sues, but Klotho deficiency impacts nearly
all tissues and organs. So, many molecular
aspects of Klotho functions remain obscure.
For instance, it is possible that some recep-
tors involved in Klotho effects are still wait-
ing to be discovered.
The antioxidant consumption associ-
ated with certain foods has proven benefits
and many researchers promote its adminis-
tration through nutraceuticals and functional
Nowadays it is clear that polyphenols are
very promiscuous molecules affecting dif-
ferent biological functions in many ways.
Indeed, growing evidence points to the fact
that under special conditions these com-
pounds could have pro-oxidant properties.
The mechanism underlying this phenome-
non has been investigated by several authors
(Arakawa
et al.
, 2002, 2004; Aragawa
et al.
,
2003; Aoshima
et al.
2005). Using green tea
catechins as a model, Arakawa and cowork-
ers (2004) demonstrated that at pH 7-8 (or
higher) such compounds could generate sig-
nificant amounts of hydrogen peroxide. The
hydrogen peroxide generation might explain
the bactericidal effect of certain flavan-3-ols
in aqueous media. Also, the production of
hydrogen peroxide has been observed in
black, green and Oolong teas with concen-
trations of 1.5 × 10
−4
, 2.4 × 10
−4
and 0.87 ×
10
−4
M, respectively. Such H
2
O
2
levels are
sufficient to exert bactericidal effects against
Gram-positive and Gram-negative bacteria
(Arakawa
et al
., 2004). Although the cyto-
protective and antioxidant abilities of these
compounds are evident in many cell lines,
in others they could induce death by apop-
tosis (Wang
et al.
, 2000a; Lu
et al.
, 2002).
This divergence has been observed, for
example, in the case of epigallocatechin gal-
late (EGCG). This compound could generate
different oxidative environments protecting
normal host cells from ROS damage and, on
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